The goal of this project is to study the gene expression of growth factors and myelin-related proteins during myelin breakdown in the central nervous system (CNS). This year we investigated the distribution of insulin-like growth factor I (IGF-1) and IGF-I receptor mRNAs and peptides during cuprizone-induced demyelination and remyelination in the CNS of young mice. Cuprizone produces primary demyelination in specific white matter regions, such as the corpus callosum and superior cerebellar peduncles by a direct toxic action on oligodendrocytes, the cells that form and maintain CNS myelin. Hybridization studies using specific nucleic acid probes and immunostaining with cell-specific markers showed that IGF-I mRNA levels increased dramatically in areas of myelin breakdown during cuprizone treatment and the IGF-I produced was localized in astrocytes. During recovery, IGF-I mRNA levels declined and there was a transient increase in IGF-I receptor mRNA and immunostaining that was localized in immature myelin-forming oligodendrocytes. This highly specific induction of IGF-I in astrocytes during demyelination and the expression of IGF-I receptor in regenerating oligodendrocytes suggest that IGF-I has an important role in regulating oligodendrocytes and myelin metabolism in vivo.